The relationship between enhanced enzyme activity and structural dynamics in ionic liquids: a combined computational...

Area of Science:

• Biocatalysis
• Enzyme kinetics
• Computational chemistry

Background:

• Candida antarctica lipase B (CALB) is a versatile enzyme used in various chemical transformations.
• Understanding CALB's behavior in different solvents is crucial for optimizing its industrial applications.
• Solvent effects on enzyme structure and activity are complex and require detailed investigation.

Purpose of the Study:

• To investigate the relationship between solvent properties and CALB activity.
• To elucidate the molecular mechanisms underlying CALB conformational changes in organic solvents and ionic liquids (ILs).
• To identify key residues and structural elements influencing CALB stability and catalytic performance.

Main Methods:

• Combined experimental and molecular dynamics (MD) simulation approaches.
• Analysis of enzyme activity assays in various solvents.
• MD simulations to observe CALB conformational dynamics and solvent interactions.
• Detailed structural analysis of the active site cavity and surrounding residues.

Main Results:

• CALB activity is directly correlated with active site cavity conformational changes, decreasing in the order [Bmim][TfO] > tert-butanol > [Bmim][Cl].
• The α-10 helix, containing ILE-285, plays a critical role in modulating the active site cavity entrance.
• Specific interactions, such as LYS-290 with chlorine anions in [Bmim][Cl], induce conformational changes (α-helix to turn) in the α-10 helix, narrowing the cavity and reducing activity.
• Electrostatic interactions between solvents and CALB correlate with observed structural changes and differences in enzyme activity.

Conclusions:

• Solvent choice significantly impacts CALB conformation, stability, and activity.
• The α-10 helix and specific residue interactions are key determinants of CALB's functional state in different media.
• Molecular dynamics simulations coupled with experimental data provide valuable insights into enzyme-solvent interactions for biocatalyst design.